tbuckley/cabot-search huggingface dataset:
GCT-16. Management of Patients with Metastatic Central Nervous System (CNS) Germinoma; A Literature Review
Authors: Mohammad Abu-Arja, Margaret Shatara, Mohamed Abdelbaki
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: Outcomes of patients with primary metastatic CNS Germinoma are excellent. There is no global consensus over the optimal irradiation doses and fields to reduce long-term radiotherapy side effects. Our literature review explores the different treatment modalities utilized for patients with metastatic CNS germinoma. METHODS: A literature review of studies that included patients with primary metastatic CNS germinoma via PubMed database. RESULTS: Sixty-eight patients (male: 48, female: 13, not specified: 7) were identified. At presentation, the median age was 14.4 years (range: 1.5–47 years). Primary tumor location included the following: pineal (n=15), suprasellar (n=11), bifocal (suprasellar and pineal) (n=21), other (n=9), not specified (n=12). Metastasis sites included the following: multifocal intracranial with/without ventricular metastasis (n=18), ventricular metastasis only (n=21), spinal metastasis only (n=8), CSF cytology dissemination only (n=3), and not specified (n=18). Seventeen patients received radiotherapy only, and 51 received radio-chemotherapy. Radiotherapy modalities included the following: craniospinal irradiation (n=36) with a mean whole-brain dose of 23.3 Gy (range:10.8-40.5 Gy) and spinal dose of 21.6 Gy (range: 10.8 – 30.6 Gy), whole-brain irradiation (n=13) with a mean dose of 24.2 Gy (range: 18 - 40 Gy), whole ventricular irradiation (n=16) with a mean dose of 24.7 Gy (range: 23.4 – 30 Gy), Focal irradiation only (n=1) with a dose of 40 Gy, and not specified (n=2). Four patients died of disease progression or relapse. Two patients were alive with relapse/residual disease. Sixty-two patients were alive with no evidence of disease with a mean follow of 77 months (range: 10.3 – 256 months). Further analysis is underway and will be presented at the meeting. CONCLUSION: The role of neoadjuvant chemotherapy in reducing the dose and field of radiation therapy remains unclear. Further analysis is pending which may highlight the role of neoadjuvant chemotherapy in managing patients with metastatic germinoma.
Machine learning approach to predict pT3a upstaging of clinically localized renal cell carcinoma and oncological outcomes after surgery (UroCCR 15 study)
Authors: A. de Hauteclocque, L. Ferrer, D. Ambrosetti, S. Ricard, P. Bigot, K. Bensalah, A. Villers, F. Henon, N. Doumerc, A. Méjean, V. Verkarre, C. Dariane, S. Larré, C. Champy, A. De La Taille, F. Bruyère, M. Rouprêt, P. Paparel, S. Droupy, A. Fontenil, J-J. Patard, R. Boissier, M. Yacoub, T. Colin, J-C. Bernhard
Journal: European Urology (2022)
Long-term medical and functional outcomes of medulloblastoma survivors: A population-based, matched cohort study.
Authors: Hallie Coltin, Priscila Pequeno, Ning Liu, Derek S. Tsang, Michael D. Taylor, Eric Bouffet, Paul C. Nathan, Vijay Ramaswamy
Journal: Journal of Clinical Oncology (2022)

10053 Background: Most medulloblastoma survivors suffer from late treatment-related sequelae. There are no population-based studies examining such late effects in a dedicated cohort of medulloblastoma survivors. Methods: Using a provincial pediatric cancer registry, all 5+ year medulloblastoma survivors diagnosed between 1987-2015 at &lt;18 years of age in Ontario, Canada were identified and matched to cancer-free population controls based on age, sex, and geographical location. Cases were followed from the index date (five years from latest of diagnosis, or relapse/subsequent malignancy prior to age 18 years) until December 31, 2020 or censorship (death, or relapse/new cancer after age 18 years). Clinical data were linked to administrative health databases to estimate the cumulative incidences and cause-specific hazard ratios (HR) of mortality, hospitalizations, strokes, hearing loss requiring a hearing aid, and receipt of homecare services between cohorts, accounting for matching and competing risks. We evaluated demographic, disease, and treatment predictors of mortality using Cox proportional hazards models. Results: Of 389 medulloblastoma diagnoses in the study period, 159 (40.9%) were excluded, most commonly due to early death prior to the index date. Two hundred thirty cases were matched to 1150 controls (Table). Ten-year survival probability after index was 92.4% in cases and 99.4% in controls (HR 21.5, 95% CI 9.8-54.0). Cases were at higher risk for hospitalizations (HR 3.4, 95% CI 2.7-4.3), stroke (HR 45.6, 95% CI 12.8-289.8), hearing loss (HR 96.3, 95% CI 39.7-317.3), and requiring homecare services (HR 7.9, 95% CI 5.8-10.9). By 10 years after index, 4.8% (95% CI 2.2-9.0) of survivors had experienced a stroke compared to 0.1% (95% CI 0.01-0.7) of controls. None of the candidate predictors were significantly associated with mortality on univariate analyses. Conclusions: Survivors of childhood medulloblastoma experienced an increased risk of mortality and serious morbidity compared to population controls. Consideration for mitigation strategies or early interventions for preventing neurovascular sequelae and hearing loss is warranted, as is dedicated supports for survivors. [Table: see text]
Liquid Biopsy for Precision Adjuvant Chemotherapy in Colon Cancer
Authors: Clara Montagut, Joana Vidal
Journal: New England Journal of Medicine (2022)

Liquid biopsy, the detection of tumor-related DNA in the peripheral blood, is currently the best available technological tool to improve clinical decision making in precision oncology.1 Liquid biopsy currently has enough analytic and clinical validity to be implemented in routine practice for advanced disease genotyping to predict the benefit of targeted drugs. An additional great promise of the measurement of circulating tumor DNA (ctDNA) has been its use for the detection of the so-called minimal residual disease, particularly after surgical therapy to remove primary tumors, as a predictor of residual disease and relapse and as an indicator of poor prognosis.2,3 . . .
AMBER parts 1c and 1e: A phase 1 study of cobolimab plus dostarlimab in patients (pts) with advanced/metastatic melanoma.
Authors: Antoni Ribas, Zeynep Eroglu, Jose Manuel Manuel Trigo Perez, Brian Di Pace, Tianli Wang, Srimoyee Ghosh, Arindam Dhar, Theo Borgovan, Angela Waszak, Diwakar Davar
Journal: Journal of Clinical Oncology (2022)

9513 Background: TIM-3 and PD-1 are markers of T-cell suppression that are upregulated in melanoma. AMBER (NCT02817633) is evaluating cobolimab (TSR-022/GSK4069889), an anti-TIM-3 therapy, monotherapy or with PD-1 inhibitors, including dostarlimab, in pts with solid tumors. Methods: This multicenter, open-label study was conducted in 2 parts: dose escalation (Parts 1 A–D and F–H) and cohort expansion (Parts 2 A–D). Part 1C and exploratory cohort 1E (reported here) included pts with advanced/metastatic melanoma; prior therapies, except for immunotherapies, were permitted. Pts received cobolimab (100 [1C only], 300, or 900 mg IV) with dostarlimab (500 mg IV) Q3W. Part 1C primary endpoints were safety, tolerability, and recommended Phase 2 dose. Objective response rate (ORR; complete [CR] or partial [PR] response per RECIST v1.1) was a secondary endpoint in 1C and the primary endpoint in 1E (ad hoc efficacy analysis reported). An integrated safety analysis for all pts (Parts 1 and 2) receiving cobolimab with dostarlimab, regardless of tumor type or cobolimab dose, is reported here. Results: 28 pts were enrolled in 1C (n=10) and 1E (n=18). Most pts (n=23; 82.1%) had cutaneous disease of the skin. One pt had anorectal mucosal disease and 3 pts in the 900-mg cohort had uveal melanoma. Most pts (67.9%) had an ECOG PS=0. At data cut-off (May 19, 2021), treatment was ongoing in 5 pts. In the integrated safety analysis of pts who received cobolimab 100 mg (n=41), 300 mg (n=167), or 900 mg (n=69) with dostarlimab, treatment-related treatment-emergent AEs (TR-TEAEs) occurred in 53.7%, 57.5%, and 59.4%, respectively. The most common TR-TEAEs (any grade, ≥10% in 100 mg, 300 mg, or 900 mg groups, respectively) were fatigue (22.0%, 13.2%, 24.6%), rash (9.8%, 5.4%, 11.6%), diarrhea (4.9%, 6.0%, 10.1%), and dyspnea (2.4%, 0%, 10.1%). Grade ≥3 TR-TEAEs occurred in 12.2% (100 mg), 10.8% (300 mg), and 20.3% (900 mg); serious TR-TEAEs occurred in 7.3%, 7.8%, and 11.6%, respectively. No pts died due to TR-TEAEs; 2.4% (100 mg), 4.2% (300 mg), and 7.2% (900 mg) discontinued due to TR-TEAEs. ORR and disease control rate (DCR: stable disease [SD] ≥16 weeks, PR, or CR) are shown in the Table. Twelve pts achieved a PR and an immune-related (ir)PR (1 in 100 mg; 8 in 300 mg; 3 in 900 mg groups). Three pts achieved SD (2 in 300 mg; 1 in 900 mg groups); 8 pts had irSD (1 in 100 mg; 4 in 300 mg; 3 in 900 mg groups). Conclusions: Cobolimab with dostarlimab showed preliminary clinical responses in pts with advanced/metastatic melanoma and an acceptable safety profile across advanced cancers. Funding: GSK (213348). Clinical trial information: NCT02817633. [Table: see text]
Lenvatinib plus hepatic arterial infusion of modified FOLFOX regime(FOHAIC) in patients with BCLC stage C hepatocellular carcinoma.
Authors: Qicong Mai, Feng Shi, Xiaoming Chen
Journal: Journal of Clinical Oncology (2022)

e16000 Background: Lenvatinib is the first-line TKI treatment for BCLC stage C hepatocellular carcinoma (HCC) with better objective response rate (ORR) and longer progression free survival (PFS) than sorafenib, but the prognosis is still unsatisfactory. Hepatic arterial infusion chemotherapy of modified FOLFOX regime (FOHAIC) has shown promising results for patients with advanced HCC. This study aimed to update the result of efficacy and safety for lenvatinib plus FOHAIC in patients with BCLC stage C hepatocellular carcinoma. Methods: This was a retrospective study including 46 patients from Nov 2018 to April 2021 Patients with BCLC stage C hepatocellular carcinoma. Patients were treated with 8 mg(≤60kg) or 12mg(&gt; 60kg) lenvatinib once daily initially and FOHAIC (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, fluorouracil bolus 400 mg/m2 on day 1, and fluorouracil infusion 2400 mg/m2 for 46 hours, every 3 weeks). Best response according to the RECIST 1.1 and mRECIST criteria. PFS, overall survival (OS) and treatment-related adverse events(TRAE) were also evaluated. Results: 46 patients(median age: 54.9 years) underwent a total of 223 cycles of HAIC therapy (mean: 4.8 cycles). 43 (93.5%) patients with HBV infection.35(76.1%). Patients were diagnosed with vascular invasion. 45 (97.8%) patients were classified as Child-pugh A class and 1 (2.2%) patients were Child-pugh B class. The ORR were 58.7% (RECIST 1.1, 27 of 46) and 76.1% (mRECIST, 35 of 46), the disease control rate (DCR) was 93.5% (RECIST 1.1/mRECIST). With a median follow-up period of 14.9 months, the median PFS and median OS were 15.9 months and 27.9 months, respectively.TRAE occurred in 36 of 46 patients (78.3%), most common TRAE were hypertension (41.3%), diarrhea (34.8%), fatigue(34.8%), abdominal pain(32.6%), hand-foot skin reaction(23.9%),and weight loss(19.6%). The grade 3/4 TRAE were more frequent in abdominal pain(8.7%), hypertension (6.5%) and diarrhea(6.5%). Conclusions: This study demonstrated that lenvatinib plus FOHAIC had acceptable toxic effects and shown promising ORR, PFS and OS in BCLC stage C hepatocellular carcinoma. Warrants its further investigation in a large-scale trial.[Table: see text]
Highlights from Recent Cancer Literature
Journal: Cancer Research (2022)

Microbiota Instructs an Immunosuppressive ResponseOnly colorectal cancers that exhibit microsatellite instability (MSI high) respond to anti-PD1/PDL1 checkpoint blockade immunotherapy (CBI).The majority of MSI low colorectal cancers are unresponsive to CBI.Investigating the APC min mouse and mouse tumor organoid models, Peuker and colleagues discovered additional T-cell checkpoints for immune resistance in colorectal cancer.Previous work identified the importance of the calcineurin-NFAT axis within cancer cells for colorectal cancer progression.This study demonstrated that calcineurin-NFAT enforced immunosuppression of antitumor CD8 þ T cells.Myeloid-derived suppressor cells of the polymorphonuclear phenotype responded to microbiota cues (e.g., LPS) to produce IL6 in a calcineurin-NFAT-dependent manner.IL6 acted on tumor cells, inducing coinhibitory molecules B7H3 and B7H4 to block the function of CD8 þ T cells.In patients with colorectal cancer, high B7H3 or B7H4 expression correlated with worse overall survival.Expert Commentary: Microbial sensing by tumor-infiltrating myeloid cells blocks T-cell responses to colorectal cancer by inducing the expression of inhibitory molecules B7H3 and B7H4 on cancer cells.
The ARVC causing TMEM43-p.S358L mutation has impact on the lipid metabolism
Authors: S Ratnavadivel, N Klinke, H Meyer, A Paululat, A Kassner, J Gummert, H Milting
Journal: Cardiovascular Research (2022)

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 450999875 Background Transmembrane protein 43 (TMEM43) is a phylogenetically highly conserved and ubiquitously expressed protein with unknown function. The protein contains four transmembrane domains located in the inner nuclear envelope and the endoplasmic reticulum (ER). A large acidic domain located between the first and second transmembrane domains, with unknown function, is exposed to the ER lumen. TMEM43-c.1073C&amp;gt;T is a rare fully penetrant mutation that leads to arrhythmogenic right ventricular cardiomyopathy type 5 (ARVC5). ARVC5 is associated with myocardial fibrosis, fibrofatty replacement and progressive loss of right ventricular myocardial tissue and severe arrhythmias causing sudden cardiac death (SCD) especially in males. The pathomechanism of ARVC5 is not well understood. Methods We isolated and cultivated primary dermal fibroblasts of three different individuals carrying TMEM43-c.1073C&amp;gt;T (p.S358L). Proteins were isolated from cell cultures and analysed by Orbitrap mass spectrometry. Proteome data of the mutation carriers were compared to TMEM43 wildtype control fibroblasts. Additionally, TMEM43-p.S358L and control fibroblasts were investigated by transmission electron microscopy (TEM). Results A total of 9 proteins were upregulated in fibroblasts expressing TMEM43-p.S358L (p&amp;lt;0.003). Of note, proteins involved in fatty acid metabolism, such as acyl-coenzym A (CoA) thioesterase 1 encoded by the gene ACOT1, and Malonate-CoA ligase encoded by ACSF3 were strongly upregulated (FC&amp;gt;3 or &amp;gt;2, respectively). ACOT1 catalyses hydrolysis acyl-CoAs to long chain fatty acids and CoA. ACSF3 catalyses the formation of thioesters between fatty acids and CoA. ACOT1 and ACSF3 regulate the intracellular levels of free fatty acids and are expressed in the cardiomyocytes of the human myocardium. TEM images of TMEM43-p.S358L carriers show an accumulation of multilamellar vesicles, which may support the dysregulation of the lipid metabolism. Conclusion The differentially regulated proteins in dermal fibroblasts and the accumulation of multilamellar vesicles suggest a dysregulation of the lipid metabolism by TMEM43-p.S358L, which may also have relevance for the development of myocardial fibrofatty replacement contributing to ARVC5.
Survival trends of patients with non‐metastatic gastric adenocarcinoma in the US and European countries: the impact of decreasing resection rates
Authors: Lei Huang, Lina Jansen, Rob H.A. Verhoeven, Jelle P. Ruurda, Liesbet Van Eycken, Harlinde De Schutter, Jan Johansson, Mats Lindblad, Tom B. Johannesen, Vesna Zadnik, Tina Žagar, Sjoerd M. Lagarde, Cornelis J.H. van de Velde, Petra Schrotz‐King, Hermann Brenner
Journal: Cancer Communications (2022)

We previously observed decreasing resection rates of non-metastatic gastric adenocarcinoma (GaC) in the US and some European countries. If and to what extent these trends affect the trends in overall survival (OS) of patients with non-metastatic GaC at the population level remain unclear. This large international population-based cohort study aimed to assess the impact of the previously observed decreasing resection rates on multivariable-adjusted trends in the long-term OS of patients with non-metastatic GaC.Individual-level data of patients with non-metastatic GaC were obtained from the national cancer registries of the Netherlands, Belgium, Sweden, Norway, and Slovenia, and the US Surveillance, Epidemiology, and End Results database. We analyzed data for each country separately. Associations between year of diagnosis and OS were assessed using Cox proportional hazards regression model with adjustment for multiple prognostic variables, with and without including resection and chemotherapy as potential explanatory variables.A total of 66,398 non-metastatic GaC patients diagnosed in 2003-2016 were analyzed, with an accumulated follow-up of 172,357 person-years. Without adjustment for resection, OS was improved only slightly in the US [hazard ratio (HR)per year = 0.99; HR≥vs.<2010 = 0.96], and no improvement was observed in the investigated European countries, with OS even worsening in Sweden (HRper year = 1.03; HR≥vs.<2010 = 1.17). After adjusting for resection, the increasing OS trend became stronger in the US (HRper year = 0.98; HR≥vs.<2010 = 0.88), and the temporal trend became insignificant in Sweden. In Slovenia (HRper year = 0.99; HR≥vs.<2010 = 0.92) and Norway (HRper year = 0.97; HR≥vs.<2010 = 0.86), improved OS over time emerged after resection adjustment. Improved OS in patients undergoing resection was observed in the US, the Netherlands, and Norway. Adjustment for chemotherapy did not alter the observed associations. Stratified analyses by tumor location showed mostly similar results with the findings in all patients with non-metastatic GaCs regarding the associations between year of diagnosis and survival.OS of patients with non-metastatic GaC mostly did not improve in selected European countries and was even worsened in Sweden, while it was slightly increased in the US in the early 21st century. Progress in OS of patients with non-metastatic GaC seems to have been impeded to a large extent by decreasing rates of resection.
Lymphocyte populations in wound fluid in breast cancer patients after mammoplasty with textured implants.
Authors: Yuriy V. Przhedetskiy, Aleksandr B. Sagakyants, Viktoria Yu Przhedetskaya, Elena Yu Zlatnik, Elena S. Bondarenko, Oksana G. Shulgina, Ekaterina I. Zolotareva, Elena P. Ulianova, Viktoria V. Pozdnyakova, Yulia V. Ulianova, Viktoriya L. Volkova, Mamuka V. Bauzhadze, Irina V. Pustovaya, Natalia A. Chertova, Elena G. Goncharova, Mary L. Maldonado
Journal: Journal of Clinical Oncology (2022)

e12588 Background: Breast reconstruction after skin-sparing mastectomy for breast cancer (BC) is an important rehabilitation stage. Its results depend on many factors, with the immune system status playing the main role. The purpose of this study was to identify characteristics of the local lymphocyte populations in patients with breast cancer in the early postoperative period after reconstructive surgery with textured implants (TI). Methods: The study included 30 patients aged 32-68 years, mean age 42.9±1.98 years, with stage I-IIb BC (monocentric nodular BC, T1N0M0 - T2N1M0). All patients underwent skin-sparing mastectomy with level II axillary lymph node dissection and immediate implant reconstruction in 2017-2019. Populations and subpopulations of lymphocytes were determined in wound fluid from the cavity with TI on days 1, 3-4 and 7 after the surgery using the FacsCanto II flow cytometer (Becton Dickinson, USA) with markers: CD3 FITC /CD15+56 PE /CD45 PerCP /CD4 PE-Cy7/CD19 APC/ CD8 APC-Cy7; CD45RA FITC /CD45RO PE /CD3 PerCP /CD8 APC; CD45RA FITC /CD62L PE /CD3 PerCP /CD4 APC; CD4 FITC /CD127 PE /CD3 PerCP / CD25 APC-Cy7; CD4 FITC /CD38PE /CD3 PerCP / HLADR APC. At least 50,000 cells were accumulated in each sample for the analysis. Results: The relative number of total lymphocytes exceeded the initial values by 3.3 (p=0.025) and 10.9 (p=0.012) times, respectively, on days 3-4 and 7 after surgery. Levels of CD3+CD4+ cells increased gradually and were 29% (p=0.042) higher by day 7, while levels of CD3+CD8+ decreased during the whole observation period. Levels of Tregs did not change, while B lymphocytes decreased by 36% (p=0.035) and 67% (p=0.026), respectively, on days 3-4 and 7. The levels of activated T lymphocytes increased by 33% (p=0.038) on days 3-4, compared with the initial values, probably due to the elevation of CD3+CD8+ levels (by 32%, p=0.037). The number of activated T lymphocytes with the CD3+CD4+ phenotype increased by 44% (p=0.024) on days 6-7. While the content of CD3+CD4+ cells with early activation markers (CD38+) significantly decreased (by 40%, p=0.031) and remained the same on days 3-4 and 7, the number of CD3+CD8+ with similar markers (CD38+) significantly increased by 28% (p=0.044) and 43%. Conclusions: TI implantation was accompanied by the activation of the cytotoxic T unit during the observation period, together with a decrease in immunosuppressive populations of lymphocytes, which may indicate a favorable development of the patient's body reaction.